Endogenous heme oxygenase/carbon monoxide system mediates lipopolysaccharide-induced intussusception in rats.

OBJECTIVES: To investigate the role of endogenous heme oxygenase (HO)/carbon monoxide (CO) system in regulating the process of intussusception (IN) induced by administration of lipopolysaccharide (LPS) in rats. METHODS: IN model of rats were induced by lipopolysaccharide. HO activity was determined by the amount of bilirubin formation which was measured with a double-beam spectrophotometer, and HbCO formation was measured by CO-oximeter. RESULTS: The results showed that LPS (10 mg/kg) caused IN in up to 40% of the rats at 6 h after each treatment of LPS. The incidence of IN were significantly increased by 50% (P < 0.05) and by 83.2% (P < 0.01) in HO substrate (heme-L-lysinate)-treated rats and in exogenous CO-treated rats, respectively; but it was sigificantly decreased by 41.8% (P < 0.05) after administration of ZnDPBG, an inhibitor of heme oxygense (HO) activity. Furthermore, LPS increased HO activity, HbCO formation cGMP content within colic smooth muscle and the plasma level of cGMP, and these parameters were significantly elevated by 62.6% (P < 0.01), 40.0% (P < 0.01), 49.3% (P < 0.05) and 38.9% (P<0.05), respectively, compared with LPS-non-IN rats. CONCLUSION: It is suggested that endogenous HO/CO system plays an important role in the process of IN induced by LPS, and inhibition of HO activity may decrease the formation of IN.

Role of endogenous carbon monoxide in neointimal formation induced by balloon-injury in rat aorta.

OBJECTIVE: The present study investigated the role of endogenous carbon monoxide (CO) in the pathogenesis of neointimal formation induced by balloon injury in rat. METHOD: Endothelial denudation of the left common carotid artery of rat was carried out by three passages of a Fogarty 2F balloon catheter. DNA, collagen and elastin contents of each intima-media were estimated; and heme oxygenase (HO) activity and CO production in vascular smooth muscle cell (VSMC) were measured after administration of HO inhibitor. RESULT: Our data showed that neointima occurred in the rat on day 7 and day 21 after balloon injury, and at the same time HO activity and CO production in VSMC were markedly increased. Administration of HO inhibitor, zinc deuteroporphyrin 2,4-bisglycol (ZnDPBG), could effectively inhibit HO activity and CO production, significantly enhance neointimal formation (aortic intima/media ratio were 21.4+/-1.8% vs 17.6+/-2.0%, P<0.05 on day 7; and 30.5+/-2.4% vs 23.0+/-2.2%, P<0.01 on day 21, respectively, compared with balloon alone group). CONCLUSION: We concluded that 1) inhibition of CO production may enhance neointimal formation induced by endothelial denudation, implying endogenous CO play an protective role in response to vascular injury, and 2) induction of HO activity may be applied clinically for preventing restenosis after angioplasty.